Intravitreal ranibizumab for the treatment of choroidal neovascularisation secondary to angioid streaks

Aims

To assess the medium to long-term efficacy and safety of intravitreal ranibizumab for the treatment of choroidal neovascularisation (CNV) secondary to angioid streaks (AS).

Methods

A total of 12 eyes of nine patients treated with intravitreal ranibizumab (0.5 mg in 0.05 ml) for CNV secondary to AS were retrospectively identified. Efficacy of treatment was determined by changes in best-corrected LogMAR visual acuity (BCVA) and optical coherence tomography. Changes with respect to baseline BCVA were defined as improved or reduced with a gain or loss of more than 10 letters, respectively, or stable if remaining within 10 letters.

Results

Over a mean follow-up of 21.75 months (range: 1–54), patients received mean 5.75 (range: 2–15) intravitreal ranibizumab injections per affected eye. BCVA improved in three eyes (25%), stabilised in eight eyes (66.67%), and deteriorated in one eye (8.33%). There was no significant change in central retinal thickness (CRT) over the follow-up period (P=0.1072). No drug-related systemic side effects were recorded.

Conclusion

The long-term treatment of CNV secondary to AS with intravitreal ranibizumab showed a stabilisation in CRT and an improvement or stabilisation of BCVA. The absence of systemic side effects was reassuring. Further long-term prospective studies are required to validate these findings.     

Intravitreal bevacizumab for the treatment of choroidal neovascularization secondary to angioid streaks: one year of follow‐up

Purpose: To evaluate the efficacy and safety of intravitreal bevacizumab at one year follow‐up, for the treatment of choroidal neovascularization (CNV) associated with angioid streaks. Methods: A retrospective case series of eighteen eyes of 17 patients with CNV secondary to angioid streaks treated with intravitreal bevacizumab between October 2006 and May 2008. Ophthalmic evaluation including best corrected visual acuity (BCVA), slit lamp biomicroscopic examination, optical coherence tomography (OCT) and fluorescein angiography, was performed before and after treatment. Retreatment was given every 4–6 weeks in case of persistent symptoms or CNV activity on OCT. Main outcome measures were changes in BCVA and central retinal thickness on OCT. Results: The mean number of injections was 4.8 at 1 year. Twelve eyes (66.6%) received five injections or more. The mean BCVA at baseline was 20/80 (range 20/400 to 20/32) and improved to 20/44 (range 20/160 to 20/20) at 1 year (p = 0.014). The BCVA improved by three or more lines in eleven eyes (61.11%) and remained within two lines of baseline in seven eyes (38.8%). Mean central retinal thickness was 404.2 μm (range 160–602 μm) at baseline and decreased to 300.5 μm (range 150–523 μm) at 1 year (p = 0.022). No ocular or systemic complications were noted. Conclusion: The 1‐year outcomes suggest intravitreal bevacizumab to be a promising treatment for CNV associated with angioid streaks, resulting in both functional and anatomical improvements. Repeated injections are needed to maintain these results. Further long term studies are required to confirm these findings.     

Crystallin distribution in Bruch's membrane-choroid complex from AMD and age-matched donor eyes

Crystallins were consistently found in a recent proteomic analysis of drusen from age-related macular degeneration (AMD) donor eyes. Here we compare the distribution of several crystallins in drusen, Bruch's membrane and choroid from AMD and non-AMD age-matched control eyes. Immunohistochemistry and Western blots of tissue samples were performed using antibodies to αA- and αB-crystallins. Bruch's membrane, drusen and the subjacent choroidal connective tissue from AMD tissues showed greater immunoreactivity for αA- and αB-crystallins than were observed in normal age-matched control tissues. Western blots also demonstrated more intense αA- and αB-crystallin signals from AMD tissues than were present in age-matched controls. These data indicate that αA- and αB-crystallins accumulate in Bruch's membrane and choroidal connective tissues to a greater degree in AMD than in normal aging. These findings suggest that the accumulation of these small heat shock proteins at this critical interface below the RPE reflects a disease-related stress response manifested during the progression of AMD.     

Transpupillary thermotherapy for the treatment of choroidal neovascularization secondary to angioid streaks

BACKGROUND: To investigate the effect of transpupillary thermotherapy (TTT) on choroidal neovascularization (CNV) secondary to angioid streaks. METHODS: Six eyes of 5 patients with an average age of 61 years were diagnosed to have subfoveal CNV secondary to angioid streaks. Four of the CNVs were predominantly classic and 2 were occult with no classic. Visual acuity (VA) measurement, ophthalmoscopic and fluorescein angiographic examination, and optic coherence tomography (OCT) were carried out before TTT treatment and at each follow-up visit. Activity scores (AS) based on clinical, angiographic, and OCT findings were also recorded. RESULTS: The mean follow-up was 12 months. The VA initially ranged from counting fingers to 20/100 and remained stable in all patients. The mean greatest lesion diameter increased significantly from 2221 microm to 3109 microm at last follow-up (p=0.046). The mean AS decreased significantly from 6.5 to 4.8 at the 3rd month (p=0.039), but tended to increase thereafter. Retreatment with TTT was applied to 5 eyes after a mean of 7.8 months but did not decrease CNV activity as effectively as the first treatments. A fibrotic scar developed in 1 eye after the first treatment. INTERPRETATION: TTT may decrease the activity of CNVs secondary to angioid streaks in the short term, but retreatment may be necessary with unfavorable results. TTT appears to stabilize VA but not lesion size in this group of patients, which may be the natural history rather than a treatment effect.     

Intravitreal aflibercept for management of subfoveal choroidal neovascularization secondary to angioid streaks

In this study, we reported the clinical results of switching from ranibizumab to aflibercept for the treatment of an insufficient responder with choroidal neovascularization (CNV) secondary to angioid streaks (AS). A 39-year-old female patient with CNV secondary to AS had bilateral persistent intraretinal and subretinal fluid on the optical coherence tomography despite prior intravitreal 0.5 mg ranibizumab injections. The therapy was switched to intravitreal injection of aflibercept. The patient received a loading dose of three intravitreal 2 mg aflibercept injections at 4-week intervals for both eyes. Morphological and functional effects were observed as early as 1-week after the first injection. After the third aflibercept injection, her visual acuity improved, intraretinal and subretinal fluid resolved, and central macular thickness reduced in both eyes. This is an early, but encouraging and promising result indicating that aflibercept might be a good alternative management for CNV secondary to AS that is insufficiently responding to prior ranibizumab injections.     

Clathrin and adaptin accumulation in drusen, Bruch's membrane and choroid in AMD and non-AMD donor eyes

Clathrin was identified in a recent proteomic analysis of Bruch's membrane from age-related macular degeneration (AMD) donor eyes. The present study was conducted to determine the localization of clathrin in AMD tissues and to compare this distribution and relative content with that in non-AMD control tissues. The distribution of adaptin, which is functionally linked to clathrin, was also evaluated. Human eyes were from donors between 66 and 94 years of age; 13 eyes were from donors with AMD and 13 from non-AMD donors. Bruch's membrane and choroid from the macula of each donor eye were prepared for immunohistochemistry and Western blotting. Differences in immunoreactivity were quantitated. Drusen, Bruch's membrane and choroid from AMD tissues showed greater immunoreactivity for clathrin and adaptin than did non-AMD tissues. Western blots also showed more intense clathrin and adaptin immunoreactivity in AMD tissues than were present in non-AMD samples. This study suggests that accumulation of clathrin and adaptin in drusen, Bruch's membrane and choroid may reflect a higher rate of clathrin mediated endocytosis in AMD tissues. Alternatively, the accumulation of these proteins in these extracellular compartments may reflect a higher susceptibility to oxidative damage.     

Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

The purpose of this study was to examine the localization and relative levels of vascular endothelial growth factor (VEGF; an angiogenic factor) and pigment epithelium-derived factor (PEDF; an antiangiogenic factor) in aged human choroid and to determine if the localization or their relative levels changed in age-related macular degeneration (AMD). Ocular tissues were obtained from eight aged control donors (age range, 75-86 years; mean age, 79.8 years) with no evidence or history of chorioretinal disease and from 12 donors diagnosed with AMD (age range, 61-105 years; mean age, 83.9 years). Tissues were cryopreserved and streptavidin alkaline phosphatase immunohistochemistry was performed with rabbit polyclonal anti-human VEGF and rabbit polyclonal anti-human PEDF antibodies. Binding of the antibodies was blocked by preincubation of the antibody with an excess of recombinant human PEDF or VEGF peptide. Choroidal blood vessels were identified with mouse anti-human CD-34 antibody in adjacent tissue sections. Three independent observers graded the immunohistochemical reaction product. The most prominent sites of VEGF and PEDF localization in aged control choroid were RPE-Bruch's membrane-choriocapillaris complex including RPE basal lamina, intercapillary septa, and choroidal stroma. There was no significant difference in immunostaining intensity and localization of VEGF and PEDF in aged control choroids. The most intense VEGF immunoreactivity was observed in leukocytes within blood vessels. AMD choroid had a similar pattern and intensity of VEGF immunostaining to that observed in aged controls. However, PEDF immunoreactivity was significantly lower in RPE cells (p=0.0073), RPE basal lamina (p=0.0141), Bruch's membrane (p<0.0001), and choroidal stroma (p=0.0161) of AMD choroids. The most intense PEDF immunoreactivity was observed in disciform scars. Drusen and basal laminar deposits (BLDs) were positive for VEGF and PEDF. In aged control subjects, VEGF and PEDF immunostaining was the most intense in RPE-Bruch's membrane-choriocapillaris complex. In AMD, PEDF was significantly lower in RPE cells, RPE basal lamina, Bruch's membrane and choroidal stroma. These data suggest that a critical balance exists between PEDF and VEGF, and PEDF may counteract the angiogenic potential of VEGF. The decrease in PEDF may disrupt the balance and be permissive for the formation of choroidal neovascularization (CNV) in AMD.     

抗VEGF药物玻璃体内注射治疗视网膜血管样条纹继发脉络膜新生血管的远期观察

目的 探讨视网膜血管样条纹继发脉络膜新生血管(choroidal neovascularization,CNV)抗VEGF治疗的远期疗效.方法 回顾分析接受玻璃体内注射抗VEGF药物的视网膜血管样条纹继发CNV患者,观察至少3 a后患者视力改善情况、视网膜及脉络膜活动性病灶消退情况等指标.结果 纳入分析的21例(30眼)患者中,眼内注射次数6 ～18(10.0±2.4)次.随访36 ～54(39.5±2.2)个月.患者首次接受治疗时BCVA为(31.00±3.81)个字母数,观察终点时最佳矫正视力为(34.00±0.35)个字母数,总体差异无统计学意义(P=o.600).患者治疗前视网膜中央厚度为(406.21±21.23) μm,随访终末时为(251.16±36.36)μm,减少值为(150.21±24.43).μm,治疗前后视网膜中央厚度比较差异有统计学意义(P =0.002).30眼中16眼在初期治疗后视力明显提升,但随访中出现病变复发活跃后视力再次下降至基线水平;10眼在病变过程中出现不同程度黄斑下萎缩及瘢痕化改变,随访过程及随访终末视力与基线视力差异均无统计学意义(均为P ＞0.05);4眼由于初始CNV未累及黄斑区,在治疗随访过程中CNV稳定.结论 由于病变的高复发性及强活跃性,抗VEGF药物治疗血管样条纹继发CNV远期预后并不理想,治疗仅发挥了一定维持视功能的作用.     

Clinical characteristics and antivascular endothelial growth factor effect of choroidal neovascularization in younger patients in Taiwan

Background/Purpose:

The purpose of this study is to share experiences diagnosing and treating choroidal neovascularization (CNV) in young patients (age ≤ 50 years) at our hospital.

Methods:

The study reviewed retrospective data of patients (≤ 50 years old) with CNV who received antivascular endothelial growth factor treatment (anti-VEGF) between January 2007 and August 2012 at Shin Kong Wu Ho-Su Memorial Hospital. We recorded the total number of injections, types of drugs, preoperative and final best-corrected visual acuity (BCVA), central retinal thickness (CRT) in optical coherence tomography (OCT), and total follow-up times, and then used two-tailed paired t tests to compare mean changes in BCVA and CRT on OCT.

Results:

The study enrolled 59 patients ≤ 50 years of age with CNV diagnosed in 67 eyes. The mean age was 36.9 ± 10.0 years (range, 8–50 years). Twenty-one patients were male and 38 patients were female. Forty-two CNV lesions were subfoveal, 19 were juxtafoveal, and five were extrafoveal. The mean total follow-up time was 18.5 ± 19.9 months (range, 0.5–71 months). Pathologic myopia was the most common cause of CNV in this study (47.8%), followed by punctate inner choroidopathy (17.9%), idiopathic CNV (16.4%), polypoidal choroidal vasculopathy (13.4%), angioid streaks (3.0%), and choroidal rupture (1.5%). After anti-VEGF treatment, the mean BCVA improved from 0.69 ± 0.61 to 0.42 ± 0.59 (p < 0.05). CRT decreased from 257.5 ± 48.2 to 210.3 ± 35.7 (p < 0.05). The mean number of injections was 1.9 ± 1.6 (range, 1–9).

Conclusion:

In this study we found that pathologic myopia, punctate inner choroidopathy, and idiopathic and polypoidal choroidal vasculopathy comprised the four most common causes of CNV in patients ≤ 50 years of age in Taiwan. We also revealed that anti-VEGF treatment is highly effective in the treatment of CNV in this age group.     

眼底血管样条纹的眼底及FFA特征分析

目的探讨[底血管样条纹(angioidstreaks,AS)的[底表现、FFA特点、并发症及预后。方法分析9例(18只[)AS患者的临床资料及[底荧光血管造影(fundusfluoresceinangiography,FFA)结果。结果①[底表现:18[后极部均可见类似血管样的放射状条纹,11[的后极部条纹通过黄斑,占61.1%,其中8[[底可见黄斑部出血、水肿、渗出等改变,占44.4%。②FFA:14[浅棕褐色的条纹均表现为强荧光带,4[桔黄色的表现为条纹中心区弱荧光,周围强荧光边;有出血、水肿等改变的区域FFA表现为动脉前期或动脉期出现边界清晰强荧光,晚期增强;或静脉期逐渐出现强荧光团,边界不清。结论大多数[底AS患者的[底所见非常典型,FFA结果有助于其病因分析、诊断分期及指导治疗。     

影像与脉络膜骨瘤

目的重新认识影像学在脉络膜骨瘤诊断中的作用。方法通过曾被影像学诊断为右脉络膜骨瘤而行眼球摘除术后，经病理诊断为右眼脉络膜血管瘤伴钙化的病例分析，结合检索了MEDI。INECD-ROM数据库（1966～2001年）与中国生物医学文献数据库（1979～2001年），并复习了1979～2001年有关脉络膜钙化、骨化和骨瘤中文文献共98篇（196例）。结果均未见经病理检查后否认的脉络膜骨瘤的报道。已报道的，其中只有5篇5例脉络膜骨瘤文献、8篇22例脉络膜骨化文献描述了病理检查结果。结论眼底窥视不清，仅有影像学诊断，未经病理证实的病例不宜确诊为脉络膜骨瘤。并提示脉络膜骨瘤、脉络膜骨化和脉络膜钙化是3个不同的概念。     

Esterified and unesterified cholesterol in drusen and basal deposits of eyes with age-related maculopathy

To address the potential for an outer segment (OS) contribution to the sub-retinal pigment epithelium (RPE) lesions of age-related maculopathy (ARM), we quantified esterified and unesterified cholesterol (EC, UC) with the sterol-specific fluorescent probe filipin in cryosections of ARM eyes. Twenty six eyes from 20 donors were preserved <5 hr after death in 4% paraformaldehyde (n = 16) or 2.5% glutaraldehyde/1% paraformaldehyde (n = 10). Eyes had exudative late ARM (n = 6), geographic atrophy (n = 15), and drusen > or =125 microm (n = 11). Sections were stained with filipin for UC or were extracted and hydrolysed with cholesterol esterase before filipin staining for EC. Drusen varied in cholesterol content, with a rough correlation between EC and UC. Dome-shaped drusen contained distinctive, loosely packed UC-rich loops. In basal deposits, EC and UC were more prominent near Bruch's membrane than near the RPE. A UC-rich material was localized within the subretinal space (n = 4). Maximum filipin fluorescence due to UC was quantified in 47 lesions (19 drusen, 24 basal deposits, and 4 sub-retinal) from 12 ARM eyes and compared to OS and inner plexiform layer (IPL) of uninvolved retina in the same sections. Relative to IPL, UC fluorescence was higher in lesions (mean+/-s.d: 1.63+/-0.69) and lower in OS (0.64+/-0.18). If only the packing of membranes explained fluorescence intensity, then one would expect much higher intensities in membrane-rich OS than in lesions. Because the converse is true, the membranous material in lesions must be more highly enriched in cholesterol on a per unit area basis. UC in sub-RPE deposits cannot be derived directly from OS without considerable intracellular processing within RPE, additional cholesterol sources, or both.     

Angioid streaks: an illustrated medical and optometric review

Angioid streaks are a rare ocular fundus finding most commonly associated with generalised elastic tissue disorders. They may be associated with a number of other systemic diseases including sickle cell anaemia, Paget's disease and the Ehlers-Danlos syndrome. However, angioid streaks also occur as an isolated finding in apparently healthy individuals. Four patients having angioid streaks are illustrated; two cases were associated with pseudoxanthoma elasticum and two had no known systemic disease. A review is presented of the clinical features of angioid streaks, together with suggestions for the management of these patients.     

弹性假黄瘤的脉络膜新生血管和血管样条纹症

目的:报告1例表现为双眼视力模糊的48岁女子患弹性假黄瘤病(pseudoxanthoma elasticum,PXE)的病例。方法:病例报告。结果:患者,女,48岁,双眼视力模糊,右眼视物变形。10a前因左眼患血管样条纹症接受激光手术,残余视力较差。右眼视力为20/60,左眼6英尺数指。眼底检查可见视网膜下出血和右侧黄斑增厚及左侧椭圆形黄斑瘢痕伴病灶萎缩性色素上皮病变。双眼有血管样条纹和橙色视网膜色素图案。外部检查发现颈部侧面和后面有几处黄色皮肤丘疹和斑块,以及明显的颏皱褶。皮肤切片病理检查证实了PXE的诊断,显示有网状真皮层深层的钙沉积和成碎片的成丛的弹性纤维。患者对玻璃体内注射贝伐单抗反应良好,右眼视力提高到20/25。强调预防保健的重要性,建议患者求助于心脏病学、胃肠病学和人类遗传学咨询服务。结论:PXE是一个累及多系统的疾病,它影响着皮肤、眼和心血管系统。在固有的皮肤变化和明显的颏皱褶的存在下,血管样条纹症和脉络膜新生血管的眼科发现能提高PXE的评估。     

Fundus Autofluorescence in Patients with Pseudoxanthoma Elasticum

Purpose: To characterize changes in fundus autofluorescence in patientswith pseudoxanthoma elasticum (PXE). Fundus autofluorescence intrinsicallyderives from lipofuscin, and the degree of autofluorescence is thought to indicatethe degree of retinal pigment epithelium (RPE) metabolic activity. Methods:Twelve eyes of 6 patients (2 men, 4 women) with PXE were studied with aconfocal scanning laser ophthalmoscope. Patient age ranged from 42 to 62years. The autofluorescence of abnormal retinal areas was compared digitallywith that of neighboring, presumed healthy control areas. When the averagegray level of a fundus region was 2 SDs above or below the average graylevel of a control area, autofluorescence of the fundus region was consideredabnormal. Results: In all 12 eyes, some segments of the angioid streaksshowed decreased fundus autofluorescence, and other segments of the streaksshowed normal autofluorescence. Areas of peripapillary chorioretinal atrophyseen in 2 eyes and of disciform scarring seen in 3 eyes showed decreasedautofluorescence. Solitary or multiple drusen-like spots showed increasedautofluorescence in all 12 eyes. Conclusion: Atrophic and degenerativeRPE regions showed decreased fundus autofluorescence in areas of chorioretinalatrophy and in some segments of the angioid streaks. Some drusen-like spotsshowed increased autofluorescence. The characteristic changes in autofluorescencethat we observed in PXE patients suggest that the content of the drusen-like substancediffers from that of senile drusen and that the drusen-like lesions are similar to thesub-RPE deposits seen in macular dystrophy.     

Choroidal neovascularization associated with coloboma of the choroid: a series of three cases

Choroidal neovascularization (CNV) is a rare complication associated with coloboma of the choroid. We describe three cases of coloboma choroid where there was loss of vision due to CNV development at the edge of the coloboma. One was managed by photodynamic therapy alone and two were managed by a combination of reduced fluence PDT and intravitreal bevacizumab. Significantly we noted that one treatment session was sufficient to achieve regression of the CNV and improvement in visual acuity.     

特发性眼底血管样条纹的临床特征

目的分析特发性眼底血管样条纹的临床特征。方法分析13例（26眼）特发性眼底血管样条纹患者的临床表现、荧光素眼底血管造影（FFA）及黄斑区光学相干断层扫描（OCT）表现。结果11眼视力≤0.3,占42.31%。26眼眼底后极部均可见类似血管样的放射状条纹,5眼为斑驳状外观,占19.23%;17眼条纹通过黄斑,占65.38%;1眼（3.8%）合并眼外伤致多发性脉络膜破裂出血。FFA显示26眼血管样条纹均表现为透见荧光,11眼黄斑区可见脉络膜新生血管（CNV）影,其亮度逐渐增强,后期有明显的荧光素渗漏。黄斑区OCT检查发现11眼有CNV表现。Ⅰ型CNV（生长于RPE光带下）：表现为在隆起的视网膜色素上皮（RPE）和脉络膜毛细血管层光带下有不均匀的中或高反射带;混合型CNV：表现为CNV侵入RPE光带及视网膜神经上皮层下空间,RPE光带中断,呈现边界不清的高反射组织。结论眼底、FFA及OCT典型表现的综合分析有助于特发性眼底血管样条纹的诊断、分期及治疗指导。     

Contractility studies on isolated bovine choroidal small arteries: determination of the active and passive wall tension-internal circumference relation

Studies on isolated choroidal arteries could help to understand the regulatory mechanisms in the choroidal circulation. The aim of the present study was therefore to assess whether contractility studies on isolated choroidal arteries were feasible and to determine the active and passive wall tension-internal circumference relation of these arteries. This relation is essential for reliable further pharmacodynamic studies on these vessels.Isolated choroidal arteries were mounted on a wire myograph for isometric tension recording. After the vessel was mounted, the L(100) (the circumference of the vessel at a transmural pressure of 100 mmHg) was determined. Then the passive and active wall tension-internal circumference relation of the choroidal vessels was obtained by stepwise increasing the internal circumference. The changes in the internal circumference were expressed as a percentage of L(100). After each increase in circumference, the passive tone (in a calcium free medium), the spontaneous tone (in a Krebs--Ringer bicarbonate solution) and the active tone (in a solution containing K(+) 120 mM and prostaglandin F(2 alpha) 30 microM) was measured. The passive tone of the vessel increased exponentially with the circumference of the vessel. Both the spontaneous tone and the active tone also increased when the vessel was stretched. They peaked when the internal circumference approached 90% of the L(100) and diminished again when the circumference was further increased. The peak value of the active tension curve averaged 2.24+/-0.47 Nm(-1) (n=10). The passive tension was 0.57+/-0.08 Nm(-1) (n=10) at this circumference. The peak value of the spontaneous tension curve averaged 0.37+/-0.08 Nm(-1) (n=10). It can be concluded that in vitro contractility studies on isolated choroidal arteries are feasible. The optimal length or preload of the choroidal arteries is attained when the internal circumference of the artery is set to 90% of the L(100).     

糖尿病患者脉络膜造影特征分析

目的：观察糖尿病患者的脉络膜循环特点,探讨糖尿病患者脉络膜循环的改变及其与DR发生发展的关系。
　　方法：选取糖尿病患者45例分为NDR、NPDR、PDR三组,并选择20例健康正常人作为对照。采用德国海德堡共焦激光眼底扫描系统对所有糖尿病患者及正常对照同步进行FFA及ICGA,对比观察两种影像特点,阐述糖尿病患者脉络膜循环病变特点。
　　结果：（1） DR各组患者视网膜中央动脉充盈时间与正常组相比无显著差异;脉络膜动脉充盈时间均较正常对照组减慢,有显著性差异（P＜0．05）。（2）各组DR患者中,病变程度越重,发生充盈倒置的比例越大。（3）随着病变程度加重,造影早期脉络膜充盈不良及晚期斑点状强荧光的比例逐渐增多。
　　结论：糖尿病患者进行ICGA揭示了脉络膜循环状态的异常,是FFA的一个重要补充,并且研究提示在DR发生之前已有脉络膜循环的异常,充分证明了糖尿病脉络膜病变的存在。